Although the role of estrogen in the etiology of ovarian cancer is uncertain, there is increasing evidence that hormone replacement therapy is a risk factor for ovarian malignancy. The production of estrogen involves the conversion of androgens via P450 aromatase, encoded by the CYP19A1 gene. Genetic variation in two CYP19A1 single-nucleotide polymorphisms (SNPs), rs749292 and rs727479, has been found to produce 10–20% increases in estrogen levels among postmenopausal women. We tested the hypothesis that these SNPs were associated with the risk of ovarian cancer in a population-based case–control study in Hawaii, including 367 histologically confirmed epithelial ovarian cancer cases and 602 age- and ethnicity-matched controls. The A allele of rs749292 was positively associated with ovarian cancer risk in a codominant model for all races combined (AG versus AA genotype: odds ratio (OR), 1.48 and 95% confidence interval (CI, 1.07–2.04); GG versus AA: OR, 1.87 (CI, 1.24–2.82); P trend=0.002). Similar significant associations of the rs749292 A allele on the risk of ovarian cancer were found among Caucasian and Japanese women. No relation of the rs727479 SNP to ovarian cancer risk was observed overall, although Caucasian women carrying the variant A allele compared with women with an CC genotype had an OR of 2.91 (CI, 1.15–7.37). These data suggest CYP19A1 variants may influence susceptibility to ovarian cancer.
Marc T Goodman, Galina Lurie, Pamela J Thompson, Katharine E McDuffie and Michael E Carney
Catherine M Olsen, Christina M Nagle, David C Whiteman, Roberta Ness, Celeste Leigh Pearce, Malcolm C Pike, Mary Anne Rossing, Kathryn L Terry, Anna H Wu, The Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, Harvey A Risch, Herbert Yu, Jennifer A Doherty, Jenny Chang-Claude, Rebecca Hein, Stefan Nickels, Shan Wang-Gohrke, Marc T Goodman, Michael E Carney, Rayna K Matsuno, Galina Lurie, Kirsten Moysich, Susanne K Kjaer, Allan Jensen, Estrid Hogdall, Ellen L Goode, Brooke L Fridley, Robert A Vierkant, Melissa C Larson, Joellen Schildkraut, Cathrine Hoyo, Patricia Moorman, Rachel P Weber, Daniel W Cramer, Allison F Vitonis, Elisa V Bandera, Sara H Olson, Lorna Rodriguez-Rodriguez, Melony King, Louise A Brinton, Hannah Yang, Montserrat Garcia-Closas, Jolanta Lissowska, Hoda Anton-Culver, Argyrios Ziogas, Simon A Gayther, Susan J Ramus, Usha Menon, Aleksandra Gentry-Maharaj and Penelope M Webb
Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case–control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m2; 95% CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.